1. Field of the Invention
The present invention relates to a method for reducing damage caused by free radicals, in particular, administering a pharmaceutical composition to a subject.
2. Description of the Prior Art
Amifostine, also called WR-2721, is the prodrug of WR-1065 with phosphate groups, and exhibits antioxidative activity. At present, drug regulatory agencies in many countries have approved the use of amifostine as a radioprotective drug for treating damage caused by radiation therapy, and the adverse effects induced by platinum-related chemotherapeutic drugs. Amifostine is spontaneously hydrolyzed in vivo, or metabolized by alkaline phosphatase through breaking up the bond between WR-1065 and its phosphate groups. The active drug, WR-1065, is then released and protects cells from damage and reduces cell toxicity by scavenging free radicals. Nonetheless, studies in patients have indicated that the distribution half-life of amifostine is less than 1 minute, and the elimination half-life is 8 minutes. Only 10% of amifostine remains 6 minutes after i.v. injection. Un-eliminated amifostine is rapidly converted to active free thiol metabolite, WR1065, and starts to function. Therefore, clinically amifostine is usually administered through i.v. injection 3 and 15 minutes before radiation therapy and chemotherapy, respectively. As a result, the most difficult problem facing the clinical application of amifostine is its short half-life.
Numerous studies and literatures have suggested that amifostine can be formulated as a slow-release or non-parenteral administration drug. Although oral administration of such formulated amifostine has been reported to prolong its half-life and increase its efficacy, none have shown better results in treating various clinical complications such as the prevention of radiation toxicity caused by nuclear plant explosion or accidental exposure, simply because no effective methods are available to control the release and selective distribution of amifostine in radio-sensitive tissues and organs.
In addition, other antioxidants may not provide long-term protection against free radicals either because it is difficult to maintain their potency or easily to be metabolized in vivo. Thus, these antioxidants may not be easily applied for protection of normal tissue from damage caused by radiation toxicity or chemotherapy.